Recent Advances in Therapy for Glioblastoma

Clarke, Jennifer; Butowski, Nicholas; Chang, Susan M.

doi:10.1001/archneurol.2010.5

Cited by 250 publications

(222 citation statements)

References 34 publications

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“…The current standard therapeutic regime includes maximal safe surgical resection combined with radiotherapy and temozolomide chemotherapy (1). Due to the development of such treatment strategies, the percentage of patients alive two years after diagnosis has increased to 26% (2). However, the prognosis of patients with glioma remains unsatisfactory.…”

Section: Introductionmentioning

confidence: 99%

All-trans retinoic acid inhibits migration, invasion and proliferation, and promotes apoptosis in glioma cells in vitro

2015

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Abstract. All-trans retinoic acid (ATRA) is a derivative of vitamin A that can induce differentiation and apoptosis, as well as inhibit proliferation, in glioma cells. However, the effect of ATRA on the migration and invasiveness of glioma remains poorly understood. In addition, although it is universally accepted that ATRA can induce apoptosis and inhibit proliferation in glioma cells, the association between the concentration and effects of ATRA remain unclear. Therefore, the present study investigated the effects of ATRA treatment on the migration, invasion, apoptosis and proliferation of glioma cells. The U87 and SHG44 glioma cell lines were treated with various concentrations of ATRA, consisting of 0, 5, 10, 20 and 40 µmol/l. A scratch wound healing assay and a Matrigel invasion assay were used to investigate cell migration and invasion, respectively. Flow cytometry was performed to investigate apoptosis and cell cycle distribution. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to investigate the expression of matrix metalloproteinase (MMP)-2 and -9 in each cell treatment group. Following treatment with ATRA, the migration, invasion and proliferation of the glioma cells were significantly inhibited, and the apoptosis rate was significantly increased compared with that of the blank control group. Furthermore, a dose-effect association was identified between each effects and ATRA treatment. The mRNA and protein expression of MMP-2 in U87 glioma cells was not significantly affected following treatment with low concentrations of ATRA, consisting of 5 and 10 µmol/l ATRA, compared with the expression in the control group (P>0.05). However, treatment with high concentrations of ATRA, consisting of 20 and 40 µmol/l ATRA, significantly downregulated the expression levels of MMP-2 in U87 cells. In contrast to U87 cells, the administration of ATRA treatment to SHG44 glioma cells resulted in a significant and dose-dependent downregulation in MMP-2 mRNA and protein expression (P<0.01). In addition, significant downregulation of MMP-9 expression was identified in the two glioma cell lines (P<0.01). The results of the present study indicate that treatment with ATRA may inhibit migration, invasion and proliferation, and promote apoptosis in glioma cells. Furthermore, the current study indicates that the inhibition of glioma cell invasion by ATRA may be partially associated with its effect ability to downregulate MMP expression.

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Section: Introductionmentioning

confidence: 99%

All-trans retinoic acid inhibits migration, invasion and proliferation, and promotes apoptosis in glioma cells in vitro

2015

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“…However, acquired resistance to the drug almost always occurs, so oncolytics armed with anticancer genes should be utilized to enhance the effects of small molecule inhibitors and to prevent development of drug resistance which will ultimately lead to disease improvement and amended clinical outcome. Research is already directed towards the use of combinatorial approaches of targeted therapies and oncolytics as clinical successes in melanoma and glioblastoma multiforme (Msaouel et al, 2013;Clarke et al, 2010;Donnelly et al, 2012;Natarajan et al, 2011) denote. We are entering an era where we possess the tools, we are able to use new technologies and the time has come to use them in our favor.…”

Section: Conclusion-future Of the Fieldmentioning

confidence: 99%

Anticancer Gene Transfer for Cancer Gene Therapy

Pazarentzos

Mazarakis

2014

Advances in Experimental Medicine and Biology

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Gene therapy vectors are among the treatments currently used to treat malignant tumors. Gene therapy vectors use a specific therapeutic transgene that causes death in cancer cells. In early attempts at gene therapy, therapeutic transgenes were driven by nonspecific vectors which induced toxicity to normal cells in addition to the cancer cells. Recently, novel cancer specific viral vectors have been developed that target cancer cells leaving normal cells unharmed. Here we review such cancer specific gene therapy systems currently used in the treatment of cancer and discuss the major challenges and future directions in this field.

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“…The newly diagnosed high-grade gliomas-like glioblastomas (GBM) are currently treated with maximum safe surgery, followed by radiotherapy (RT), and/or systemic chemotherapy (CT) [1]. Due to the development of such standard treatment strategies, the percentage of patients alive two years after diagnosis has increased to 26% [2]. However, the majority of glioblastoma patients, particularly the elderly, succumb to the disease within a year [3], and this is not satisfactory.…”

Section: Introductionmentioning

confidence: 99%

The Effects of All-Trans Retinoic Acid on Vasculogenic Mimicry Formation Ability in CD133+ Glioma Stem Cells and Its Mechanisms

Tang¹,

Chen²,

Shangguan³

et al. 2017

JBM

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Objective: to investigate the effects of all-trans retinoic acid (ATRA) on vasculogenic mimicry formation in glioma stem cells. Methods: U87 stem cells were harvested through a suspension culture assay from the U87 cells, identified by CD133 and nestin, and counted by a flow cytometry. To investigate the VM formation ability of U87 stem cells with the treatment of various concentrations of ATRA, a Matrigel-based tube formation assay was used in the present study in vitro and tube-like structure (typical tube, TT; atypical tube AT) was observed and counted. Then the expressions of VEGF, VEGFR-2 and CD133 were measured throughout real time q-PCR, western blotting and immunofluorescence techniques. The data, presented as the mean ± standard deviation, were analyzed using SPSS software. One-way analysis of variance was used to compare groups and Fisher's least significant difference tests were performed for subsequent comparisons between groups. P < 0.01 was considered to indicate a statistically significant difference. Results: Most of the harvested spheroid cells were positive for nestin and 88.4% were positive forCD133. The CD133+ U87 cells were cultured into tube like structure loaded on the top of Matrigel and the quantity of tubes was decreased under the treatment of ATRA. In addition, the expressions of VEGF, VEGFR-2 and CD133 were significantly reduced under the treatment of ATRA, particularly in the higher concentration groups (20 and 40 µmol, P < 0.01). Conclusions: ATRA may inhibit the establishment of VM differing from stem cells in glioma, and these effects may attribute to the effects of ATRA's promotion of the differentiation of stem cells and/or down regulation of the expressions of proangiogenic factors VEGF and its receptor VEGFR-2. Thus, the results of the present study indicated a novel idea for the treatment of GBM and

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Recent Advances in Therapy for Glioblastoma

Cited by 250 publications

References 34 publications

All-trans retinoic acid inhibits migration, invasion and proliferation, and promotes apoptosis in glioma cells in vitro

All-trans retinoic acid inhibits migration, invasion and proliferation, and promotes apoptosis in glioma cells in vitro

Anticancer Gene Transfer for Cancer Gene Therapy

The Effects of All-Trans Retinoic Acid on Vasculogenic Mimicry Formation Ability in CD133+ Glioma Stem Cells and Its Mechanisms

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